dbSNP rs999842: CYFIP1:c.3597+29A>G (chr15-22872796-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014608.6(CYFIP1):c.3597+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,608,006 control chromosomes in the GnomAD database, including 249,610 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20599 hom., cov: 32)

Exomes 𝑓: 0.56 ( 229011 hom. )

Consequence

CYFIP1
NM_014608.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

Publications

20 publications found

Variant links:

Genes affected

CYFIP1 (HGNC:13759): (cytoplasmic FMR1 interacting protein 1) This gene encodes a protein that regulates cytoskeletal dynamics and protein translation. The encoded protein is a component of the WAVE regulatory complex (WRC), which promotes actin polymerization. This protein also interacts with the synaptic functional regulator FMR1 protein and translation initiation factor 4E to inhibit protein translation. A large chromosomal deletion including this gene is associated with increased risk of schizophrenia and epilepsy in human patients. Reduced expression of this gene has been observed in various human cancers and the encoded protein may inhibit tumor invasion. [provided by RefSeq, Mar 2022]

CYFIP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6 link	c.3597+29A>G		intron_variant	Intron 30 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5 link	c.3597+29A>G		intron_variant	Intron 30 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78099

AN:

151868

Hom.:

20598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.490

GnomAD2 exomes

AF:

0.552

AC:

138260

AN:

250408

AF XY:

0.555

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.648

Gnomad FIN exome

AF:

0.662

Gnomad NFE exome

AF:

0.567

Gnomad OTH exome

AF:

0.544

GnomAD4 exome

AF:

0.558

AC:

812410

AN:

1456020

Hom.:

229011

Cov.:

AF XY:

0.558

AC XY:

404613

AN XY:

724568

show subpopulations

African (AFR)

AF:

0.383

AC:

12797

AN:

33388

American (AMR)

AF:

0.486

AC:

21693

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

10610

AN:

26080

East Asian (EAS)

AF:

0.594

AC:

23563

AN:

39648

South Asian (SAS)

AF:

0.564

AC:

48515

AN:

86006

European-Finnish (FIN)

AF:

0.653

AC:

34856

AN:

53346

Middle Eastern (MID)

AF:

0.429

AC:

2467

AN:

5752

European-Non Finnish (NFE)

AF:

0.565

AC:

625325

AN:

1106946

Other (OTH)

AF:

0.541

AC:

32584

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

16845

33689

50534

67378

84223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17360

34720

52080

69440

86800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.514

AC:

78129

AN:

151986

Hom.:

20599

Cov.:

AF XY:

0.519

AC XY:

38537

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.392

AC:

16266

AN:

41446

American (AMR)

AF:

0.488

AC:

7447

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1435

AN:

3468

East Asian (EAS)

AF:

0.630

AC:

3253

AN:

5166

South Asian (SAS)

AF:

0.584

AC:

2808

AN:

4810

European-Finnish (FIN)

AF:

0.662

AC:

6983

AN:

10552

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.563

AC:

38282

AN:

67970

Other (OTH)

AF:

0.488

AC:

1030

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1887

3773

5660

7546

9433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.543

Hom.:

21557

Bravo

AF:

0.499

Asia WGS

AF:

0.536

AC:

1859

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.17

(source)

DANN

Benign

0.44

PhyloP100

-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over